Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth

Murali Gururajan, Trivikram Dasu, Seif Shahidain, C. Darrell Jennings, Darrell A. Robertson, Vivek M. Rangnekar, Subbarao Bondada

Research output: Contribution to journalArticlepeer-review

70 Scopus citations

Abstract

Curcumin (diferuloylmethane), a component of dietary spice turmeric (Curcuma longa), has been shown in recent studies to have therapeutic potential in the treatment of cancer, diabetes, arthritis, and osteoporosis. We investigated the ability of curcumin to modulate the growth of B lymphomas. Curcumin inhibited the growth of both murine and human B lymphoma in vitro and murine B lymphoma in vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma is through inhibition of the survival kinase Akt and its key target Bad. However, in vitro kinase assays show that Akt is not a direct target of curcumin. We identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase (Syk). Syk is constitutively activated in primary tumors and B lymphoma cell lines and curcumin down-modulates Syk activity accompanied by down-regulation of Akt activation. Moreover, we show that overexpression of Akt, a target of Syk, or Bcl-xL, a target of Akt can overcome curcumin-induced apoptosis of B lymphoma cells. These observations suggest a novel growth promoting role for Syk in lymphoma cells.

Original languageEnglish
Pages (from-to)111-121
Number of pages11
JournalJournal of Immunology
Volume178
Issue number1
DOIs
StatePublished - Jan 1 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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